Atorvastatin, L-Carnitine and Non-Alcoholic Steatohepatitis (NALCAT)

Comparison the Effectiveness of L-Carnitine With Atorvastatin in Non-Alcoholic Steatohepatitis (NASH)

The aim of the present study was to compare the effects of simvastatin and L-carnitine coadministration versus simvastatin, L-Carnitine monotherapy on liver transaminases and liver elasticity in NASH patients.

Study Overview

• Status: Unknown
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Atorvastatin; Drug: L-Carnitine; Drug: Placebo

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from steatosis to steatohepatitis (nonalcoholic steatohepatitis, NASH) to cirrhosis. Statins are competitive inhibitors of Hydroxymethylglutaryl-CoA reductase, the rate-limiting step in cholesterol biosynthesis. They occupy a portion of the binding site of Hydroxymethylglutaryl-CoA, blocking access of this substrate to the active site on the enzyme. A reduction in intrahepatic cholesterol leads to an increase in LDL receptor turnover that results from an enhanced rate of hepatic LDL receptor cycling. On the other hand recent studies have implicated several important cellular processes and signaling pathways that are affected by abnormal lipid metabolism, resulting in specific biochemical, histological, and clinical changes associated with NAFLD.

Maybe statins, as lipid lowering agents, and through their effect in reduction of intrahepatic cholesterol, can affect the abnormal lipid metabolism in NASH.

L- carnitine, can improve the outcome of NASH, because it reduces lipid levels, limits oxidative stress, and modulates inflammatory responses . It performs a number of essential intracellular and metabolic functions, such as fatty acid transport, detoxification of potentially toxic metabolites, regulation of the mitochondrial acyl-CoA / CoA ratio, and stabilization of cell membranes. It has a pivotal role in the transport of long chain fatty acids across the inner mitochondrial membrane.

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shahin Merat, Professor; Phone Number: +98 917 117 3966; Email: merat@tums.ac.ir
• Study Contact Backup: Name: Reza Malekzadeh, Professor; Phone Number: +98 912 111 4139; Email: malek@ams.ac.ir

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 14117
    • Recruiting
    • Masoud Clinic
    • Contact: Shahin Merat; Phone Number: +989171173966; Email: shahin.merat@gmail.com
  • Fars
    • Shiraz, Fars, Iran, Islamic Republic of
      • Active, not recruiting
      • Pars Cohort Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• NASH diagnosed on the basis of the following criteria:

  1. Imaging techniques showing evidence of hepatic steatosis
  2. Increased alanine transaminase above 1.5 times normal (normal: 20 IU/L for women, 30 for men) on two occasions three months apart.

Exclusion Criteria:

• Patients with hepatitis B or C
• alanine transaminase > 300 IU/L
• Participants presenting one or more causes commonly associated with secondary NAFLD (drugs, surgical procedures, environmental toxins, or total parenteral nutrition)
• Alcohol ingestion greater than 40 gr per week
• Abnormal Lipid profile (TG>500 , LDL>160)
• Patients with hypertension, diabetes mellitus, coronary heart disease
• Fibroscan score more than 14 kp
• pregnancy, lactation
• Drug addiction
• Reynolds Risk Score > 10%
• Not consenting to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; 20mg atorvastatin daily	Drug: Atorvastatin; Atorvastatin 20 mg
Experimental: Carnitine; 1000mg L-carnitine daily	Drug: L-Carnitine; 1000mg L-carnitine
Experimental: Atoral; 1000mg L-carnitine and 20mg atorvastatin	Drug: Atorvastatin; Atorvastatin 20 mg; Drug: L-Carnitine; 1000mg L-carnitine
Placebo Comparator: Placebo; Identically looking placebo	Drug: Placebo; Identically looking placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement in liver stiffness	As measured by Fibroscan	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement in liver enzyme levels	Difference between last and first measurements	2 years
Adverse drug events	questionnaire	2 years

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: June 8, 2012
• First Submitted That Met QC Criteria: June 8, 2012
• First Posted (Estimate): June 12, 2012

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 5, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Non-alcoholic steatohepatitis, Atorvastatin, L-Carnitine
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 90-03-37-15428